Implication of HCN channels in the frontal cortex on the emotional abnormality of mice induced by exposure to a single restraint stress

[Speaker] Kazuhiro Kurokawa:1
[Co-author] Kazuya Miyagawa:1, Atsumi Saito:1, Hiroko Miyagishi:1, Minoru Tsuji:1, Hiroshi Takeda:1
1:Pharmacology, School of Pharmacy International University of Health and Welfare, Japan

 Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is thought to be essential regulators of neuronal excitability. On the other hand, our previous data demonstrated that stress-adaptive and -maladaptive models could be developed by repeatedly exposure to different degrees of restraint stress in mice. As a first step to clarify the relationship between HCN and stress-adaptive and maladaptation, the present study investigated the role of brain HCN on the emotional responses after a single exposure to restraint stress in mice.
 Immediately after a single exposure to restraint stress for 60 min, the emotionality of mice was estimated by the hole-board test. To explore the roles of HCN channels on the acute emotional stress responses of mice, the selective HCN channel antagonist ZD7288 was intracerebroventricularly administered 30 min before exposed to a single restraint stress. After the behavioral experiment is completed, different brain regions (frontal cortex, hippocampus, and hypothalamus) were dissected to measure the cAMP activity and the level of p-CaMKII (Thr286) protein.
 A single exposure to restraint stress for 60 min induced significant decrease in the number and duration of head-dipping behaviors in the hole-board test. Under these conditions, the decrease in head-dipping behaviors was significantly inhibited by pretreatment with ZD7288. Intracellular cAMP levels in the frontal cortex were increased by a single exposure to restraint stress for 60 min, whereas no changes were observed in the hippocampus and hypothalamus. Western blot analysis revealed that the expression level of p-CaMKII (Thr286) was significantly decreased in the frontal cortex of mice exposed to restraint stress for 60 min, and this change was inhibited by pretreatment with ZD7288.
 These findings suggest that cAMP-mediated activation of HCN channels may be involved, at least in part, in the expression of acute emotional stress responses by suppressing phosphorylation of CaMKII protein in the frontal cortex in mice.

Advanced Search